CART attenuates endoplasmic reticulum stress response induced by cerebral ischemia and reperfusion through upregulating BDNF synthesis and secretion.

CART attenuates endoplasmic reticulum stress response induced by cerebral ischemia and reperfusion through upregulating BDNF synthesis and secretion.
Biochem Biophys Res Commun. 2013 Jun 13;
Authors: Qiu B, Hu S, Liu L, Chen M, Wang L, Zeng X, Zhu S
Abstract
Cocaine and amphetamine regulated transcript (CART), a neuropeptide, has shown strong neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury in vivo and in vitro. Here, we report a new effect of CART on ER stress which is induced by cerebral I/R in a rat model of middle cerebral artery occlusion (MCAO) or by oxygen and glucose deprivation (OGD) in cultured cortical neurons, as well as a new functionality of BDNF in the neuroprotection by CART against the ER stress in cerebral I/R. The results showed that CART was effective in reducing the neuronal apoptosis and expression of ER stress markers (GRP78, CHOP and cleaved caspase12), and increasing the BDNF expression in I/R injury rat cortex both in vivo and in vitro. In addition, the effects of CART on ischemia-induced neuronal apoptosis and ER stress were suppressed by tyrosine receptor kinase B (TrkB) IgG, whereas the effects of CART on BDNF transcription, synthesis and secretion were abolished by CREB siRNA. This work suggests that CART is functional in inhibiting the cerebral I/R-induced ER stress and neuronal apoptosis by facilitating the transcription, synthesis and secretion of BDNF in a CREB-dependent way.
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Source: Biochemical and Biophysical Research communications - June 13, 2013 Category: Biochemistry Authors: Qiu B, Hu S, Liu L, Chen M, Wang L, Zeng X, Zhu S Tags: Biochem Biophys Res Commun Source Type: research